Tumors are dependent upon new blood vessel formation, or angiogenesis, for expansive growth. Our recent analysis of gene expression led to the identification of several genes upregulated in endothelial cells that line tumor blood vessels, called Tumor endothelial markers (TEMs). However, further investigation of these genes has revealed that most are also present during normal physiological angiogenesis, for example, during wound healing and corpus luteum formation. In order to identify TEMs that are more confined to tumor endothelium, we plan to compare gene expression patterns of endothelial cells isolated from either regenerating liver (normal physiological angiogenesis) or liver metastasis (tumor angiogenesis). Towards this end, we have recently developed techniques that have enabled us to isolate endothelial cells from these tissues in mice. We will use Serial Analysis of Gene Expression (SAGE) technology to compare gene expression profiles, and then compare lead candidates to our human endothelial cell SAGE libraries to identify those which are also overexpressed in human tumor endothelium. These studies should enable us to identify new targets of tumor blood vessels that, hopefully, will have fewer cross reactivity's to normal tissues.